Dena Dubal, MD, PhD

Assoc Professor in Residence
Neurology
+1 415 502-7237

The goal of our research is to investigate mechanisms of longevity, resilience and neurodegenerative disease. Broadly we investigate how aging pathways can confer resilience to a brain and counter neurodegenerative diseases like Alzheimer’s. Using genetic mouse models, cell culture methods, and study of human populations using cutting-edge techniques, we study whether longevity-derived mechanisms can pave a path toward development of urgently needed therapies in aging and disease.

To this end, we are unraveling mechanisms that underlie female longevity, studying sex chromosomal contributions to neurodegenerative disease, and investigating the longevity hormone klotho in the normal and diseased brain.

Publications: 

An Integrated Analysis of Clinical, Genomic, and Imaging Features Reveals Predictors of Neurocognitive Outcomes in a Longitudinal Cohort of Pediatric Cancer Survivors, Enriched with CNS Tumors (Rad ART Pro).

Frontiers in oncology

Kline C, Stoller S, Byer L, Samuel D, Lupo JM, Morrison MA, Rauschecker AM, Nedelec P, Faig W, Dubal DB, Fullerton HJ, Mueller S

KL1 domain of longevity factor klotho mimics the metabolome of cognitive stimulation and enhances cognition in young and aging mice.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Gupta S, Moreno AJ, Wang D, Leon J, Chen C, Hahn O, Poon Y, Greenberg K, David N, Wyss-Coray T, Raftery D, Promislow DEL, Dubal DB

Deep phenotyping of Alzheimer's disease leveraging electronic medical records identifies sex-specific clinical associations.

Nature communications

Tang AS, Oskotsky T, Havaldar S, Mantyh WG, Bicak M, Solsberg CW, Woldemariam S, Zeng B, Hu Z, Oskotsky B, Dubal D, Allen IE, Glicksberg BS, Sirota M

KIBRA, MTNR1B, and FKBP5 genotypes are associated with decreased odds of incident delirium in elderly post-surgical patients.

Scientific reports

Terrelonge M, LaHue SC, Tang C, Movsesyan I, Pullinger CR, Dubal DB, Leung J, Douglas VC

Female resilience in brain aging.

Innovation in Aging

Dena Dubal

Sex-Stratified Single-Cell RNA-Seq Analysis Identifies Sex-Specific and Cell Type-Specific Transcriptional Responses in Alzheimer's Disease Across Two Brain Regions.

Molecular neurobiology

Belonwu SA, Li Y, Bunis D, Rao AA, Solsberg CW, Tang A, Fragiadakis GK, Dubal DB, Oskotsky T, Sirota M

Sex-Specific Association of the X Chromosome With Cognitive Change and Tau Pathology in Aging and Alzheimer Disease.

JAMA neurology

Davis EJ, Solsberg CW, White CC, Miñones-Moyano E, Sirota M, Chibnik L, Bennett DA, De Jager PL, Yokoyama JS, Dubal DB

Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease.

Frontiers in Endocrinology

Gaitán JM, Moon HY, Stremlau M, Dubal DB, Cook DB, Okonkwo OC, van Praag H

Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes.

Journal of Alzheimer's disease : JAD

Driscoll I, Ma Y, Gallagher CL, Johnson SC, Asthana S, Hermann BP, Sager MA, Blennow K, Zetterberg H, Carlsson CM, Engelman CD, Dubal DB, Okonkwo OC

Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes.

Journal of Alzheimer's disease : JAD

Driscoll I, Ma Y, Gallagher CL, Johnson SC, Asthana S, Hermann BP, Sager MA, Blennow K, Zetterberg H, Carlsson CM, Engelman CD, Dubal DB, Okonkwo OC

QOL-53. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS.

Neuro-Oncology

Cassie Kline, Schuyler Stoller, Lennox Byer, Caleb Edwards, Rachna Prasad, Joseph Torkildson, Karen Gauvain, David Samuel, Janine Lupo, Melanie Morrison, Elizabeth Tong, Solomiia Savchuk, Christian Rodrigo Ugaz Valencia, Andreas Rauschecker, Jeffrey Rudie, Thomas Hoffman, Dena Dubal, Heather Fullerton, Sabine Mueller

NCOG-71. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS.

Neuro-Oncology

Cassie Kline, Schuyler Stoller, Lennox Byer, Caleb Edwards, Rachna Prasad, Joseph Torkildson, Karen Gauvain, David Samuel, Janine Lupo, Melanie Morrison, Elizabeth Tong, Solomiia Savchuk, Christian Rodrigo Ugaz Valencia, Andreas Rauschecker, Jeffrey Rudie, Thomas Hoffmann, Dena Dubal, Heather Fullerton, Sabine Mueller

A second X chromosome contributes to resilience in a mouse model of Alzheimer's disease.

Science translational medicine

Davis EJ, Broestl L, Abdulai-Saiku S, Worden K, Bonham LW, Miñones-Moyano E, Moreno AJ, Wang D, Chang K, Williams G, Garay BI, Lobach I, Devidze N, Kim D, Anderson-Bergman C, Yu GQ, White CC, Harris JA, Miller BL, Bennett DA, Arnold AP, De Jager PL, Palop JJ, Panning B, Yokoyama JS, Mucke L, Dubal DB

4329 Investigating the role of Klotho in neurocognitive outcomes, brain volumes, and white matter changes in pediatric brain tumor survivors.

Journal of Clinical and Translational Science

Caleb Simpeh Edwards, Schuyler Stoller, Sol Savchuk, Christian Rodrigo Ugaz Valencia, Liz Tong, Andreas Rauschecker, Dena Dubal, Cassie Kline, Sabine Mueller

Sexual dimorphism of physical activity on cognitive aging: Role of immune functioning.

Brain, behavior, and immunity

Casaletto KB, Lindbergh C, Memel M, Staffaroni A, Elahi F, Weiner-Light S, You M, Fonseca C, Karydas A, Jacobs E, Dubal DB, Yaffe K, Kramer JH

Pathways to brain resilience.

Nature medicine

Dubal DB

KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD.

Neurology

Erickson CM, Schultz SA, Oh JM, Darst BF, Ma Y, Norton D, Betthauser T, Gallagher CL, Carlsson CM, Bendlin BB, Asthana S, Hermann BP, Sager MA, Blennow K, Zetterberg H, Engelman CD, Christian BT, Johnson SC, Dubal DB, Okonkwo OC

Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults.

Neurobiology of aging

Casaletto KB, Elahi FM, Staffaroni AM, Walters S, Contreras WR, Wolf A, Dubal D, Miller B, Yaffe K, Kramer JH

Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice.

eNeuro

Broestl L, Worden K, Moreno AJ, Davis EJ, Wang D, Garay B, Singh T, Verret L, Palop JJ, Dubal DB

QOL-47. ApoE4 AS A GENETIC PREDICTOR FOR NEUROCOGNITIVE OUTCOMES IN PEDIATRIC BRAIN TUMOR SURVIVORS.

Neuro-Oncology

Cassie Kline, Erin Felton, Lennox Byer, Schuyler Stoller, Joseph Torkildson, Karen Gauvain, David Samuel, Elizabeth Tong, John Liu, Heather Fullerton, Dena Dubal, Sabine Mueller

The Way of Tau: Secretion and Synaptic Dysfunction.

Trends in molecular medicine

Dubal DB

Cord blood klotho levels are inversely associated with leptin in healthy Latino neonates at risk for obesity.

Journal of pediatric endocrinology & metabolism : JPEM

Wojcicki JM, Prather AA, Epel E, Wang D, Dubal DB

Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and a-Synuclein Transgenic Mice.

Cell reports

Leon J, Moreno AJ, Garay BI, Chalkley RJ, Burlingame AL, Wang D, Dubal DB

BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention.

Neurology

Boots EA, Schultz SA, Clark LR, Racine AM, Darst BF, Koscik RL, Carlsson CM, Gallagher CL, Hogan KJ, Bendlin BB, Asthana S, Sager MA, Hermann BP, Christian BT, Dubal DB, Engelman CD, Johnson SC, Okonkwo OC

Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging.

Brain imaging and behavior

Yokoyama JS, Marx G, Brown JA, Bonham LW, Wang D, Coppola G, Seeley WW, Rosen HJ, Miller BL, Kramer JH, Dubal DB

Sex biology contributions to vulnerability to Alzheimer's disease: A think tank convened by the Women's Alzheimer's Research Initiative.

Alzheimer's & dementia : the journal of the Alzheimer's Association

Snyder HM, Asthana S, Bain L, Brinton R, Craft S, Dubal DB, Espeland MA, Gatz M, Mielke MM, Raber J, Rapp PR, Yaffe K, Carrillo MC

LONGEVITY GENE KLOTHO ALTERS APOE4-RELATED CORTICAL THINNING: FINDINGS FROM THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION.

Alzheimer's & Dementia

Stephanie A. Schultz, Elizabeth A. Boots, Jennifer M. Oh, Burcu F. Darst, Rebecca L. Koscik, Catherine L. Gallagher, Cynthia M. Carlsson, Howard A. Rowley, Barbara B. Bendlin, Sanjay Asthana, Mark A. Sager, Kirk J. Hogan, Bruce P. Hermann, Corinne D. Engelman, Sterling C. Johnson, Dena B. Dubal, Ozioma C. Okonkwo

LONGEVITY GENE KLOTHO ALTERS APOE4-RELATED CORTICAL THINNING: FINDINGS FROM THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION.

Alzheimer's & Dementia

Stephanie A. Schultz, Elizabeth A. Boots, Jennifer M. Oh, Burcu F. Darst, Rebecca L. Koscik, Catherine L. Gallagher, Cynthia M. Carlsson, Howard A. Rowley, Barbara B. Bendlin, Sanjay Asthana, Mark A. Sager, Kirk J. Hogan, Bruce P. Hermann, Corinne D. Engelman, Sterling C. Johnson, Dena B. Dubal, Ozioma C. Okonkwo

Network dysfunction in a-synuclein transgenic mice and human Lewy body dementia.

Annals of clinical and translational neurology

Morris M, Sanchez PE, Verret L, Beagle AJ, Guo W, Dubal D, Ranasinghe KG, Koyama A, Ho K, Yu GQ, Vossel KA, Mucke L

Longevity factor klotho and chronic psychological stress.

Translational psychiatry

Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, Dubal DB

Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Dubal DB, Zhu L, Sanchez PE, Worden K, Broestl L, Johnson E, Ho K, Yu GQ, Kim D, Betourne A, Kuro-O M, Masliah E, Abraham CR, Mucke L

Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory.

Nature neuroscience

Orr AG, Hsiao EC, Wang MM, Ho K, Kim DH, Wang X, Guo W, Kang J, Yu GQ, Adame A, Devidze N, Dubal DB, Masliah E, Conklin BR, Mucke L

Variation in longevity gene KLOTHO is associated with greater cortical volumes.

Annals of clinical and translational neurology

Yokoyama JS, Sturm VE, Bonham LW, Klein E, Arfanakis K, Yu L, Coppola G, Kramer JH, Bennett DA, Miller BL, Dubal DB

Life extension factor klotho enhances cognition.

Cell reports

Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-o M, De Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L

Reversible suppression of electrocerebral activity.

The Neurohospitalist

Broestl L, Cornes S, Dubal DB

T-cell lymphoproliferative disorder following mycophenolate treatment for myasthenia gravis.

Muscle & nerve

Dubal DB, Mueller S, Ruben BS, Engstrom JW, Josephson SA

Collagen VI protects neurons against Abeta toxicity.

Nature neuroscience

Cheng JS, Dubal DB, Kim DH, Legleiter J, Cheng IH, Yu GQ, Tesseur I, Wyss-Coray T, Bonaldo P, Mucke L

P1-465: Role of collagen VI in Alzheimer's disease: Potential mechanisms of protection.

Alzheimer's & Dementia

Dena B. Dubal, Jason Cheng, Justin Legleiter, Sarah Wilkins, Paolo Bonaldo, Gui-Qiu Yu, Lennart Mucke

A case of paraneoplastic myelopathy associated with the neuromyelitis optica antibody.

Nature clinical practice. Neurology

Mueller S, Dubal DB, Josephson SA

Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERalpha in estradiol-mediated protection against delayed cell death.

Endocrinology

Dubal DB, Rau SW, Shughrue PJ, Zhu H, Yu J, Cashion AB, Suzuki S, Gerhold LM, Bottner MB, Dubal SB, Merchanthaler I, Kindy MS, Wise PM

Stroke injury in rats causes an increase in activin A gene expression which is unaffected by oestradiol treatment.

Journal of neuroendocrinology

Böttner M, Dubal DB, Rau SW, Suzuki S, Wise PM

Activin gene expression increases after stroke injury: Modulation by estradiol.

Experimental and Clinical Endocrinology & Diabetes

M Böttner, DB Dubal, SW Rau, PM Wise

Are Estrogens Protective or Risk Factors in the Brain? Insights Derived From Animal Models.

Endocrine Aspects of Successful Aging: Genes, Hormones and Lifestyles

Phyllis M. Wise, Dena B. Dubal

Mechanisms of sex-based neuropathologies.

Principles of Sex-based Differences in Physiology

Phyllis M. Wise, Dena B. Dubal, Shane W. Rau, Adrienne B. Cashion

Estradiol attenuates programmed cell death after stroke-like injury.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Rau SW, Dubal DB, Böttner M, Gerhold LM, Wise PM

Estradiol differentially regulates c-Fos after focal cerebral ischemia.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Rau SW, Dubal DB, Böttner M, Wise PM

Estrogen and neuroprotection: from clinical observations to molecular mechanisms.

Dialogues in clinical neuroscience

Dubal DB, Wise PM

Neuroendocrine modulation and repercussions of female reproductive aging.

Recent progress in hormone research

Wise PM, Smith MJ, Dubal DB, Wilson ME, Rau SW, Cashion AB, Böttner M, Rosewell KL

Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies.

Brain research. Brain research reviews

Wise PM, Dubal DB, Wilson ME, Rau SW, Böttner M, Rosewell KL

In Vitro and In Vivo Approaches to the Study of the Neuroprotective Actions of Estradiol.

Neuroplasticity, Development, and Steroid Hormone Action

Phyllis Wise, Melinda Wilson, Dena Dubal, Shane Rau

Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action.

Endocrinology

Wise PM, Dubal DB, Wilson ME, Rau SW, Böttner M

Estrogen receptor a, not ß, is a critical link in estradiol-mediated protection against brain injury.

Proceedings of the National Academy of Sciences

Dena B. Dubal, Hong Zhu, Jin Yu, Shane W. Rau, Paul J. Shughrue, Istvan Merchenthaler, Mark S. Kindy, Phyllis M. Wise

Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury.

Proceedings of the National Academy of Sciences of the United States of America

Dubal DB, Zhu H, Yu J, Rau SW, Shughrue PJ, Merchenthaler I, Kindy MS, Wise PM

Estrogens: trophic and protective factors in the adult brain.

Frontiers in neuroendocrinology

Wise PM, Dubal DB, Wilson ME, Rau SW, Liu Y

Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury.

Journal of neurocytology

Wise PM, Dubal DB, Wilson ME, Rau SW

Neuroprotective actions of estradiol in the adult and aging brain: Potential mechanisms of action.

Neurobiology of aging

Phyllis M. Wise, Dena Dubal, Melinda E. Wilson, Shane W. Rau

Estradiol: a protective and trophic factor in the brain.

Journal of Alzheimer's disease : JAD

Dubal DB, Wilson ME, Wise PM

Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Dubal DB, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM

Neuroendocrine influences and repercussions of the menopause.

Endocrine reviews

Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL

Estradiol protects against ischemic injury.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Dubal DB, Kashon ML, Pettigrew LC, Ren JM, Finklestein SP, Rau SW, Wise PM